mTOR signaling and Alzheimer's disease: What we know and where we are?
Samin Davoody1, Afsaneh Asgari Taei2, Pariya Khodabakhsh3
1Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Despite the great body of research done on Alzheimer's disease, the underlying mechanisms have not been vividly investigated. To date, the accumulation of amyloid-beta plaques and tau tangles constitutes the hallmark of the disease; however, dysregulation of the mammalian target of rapamycin (mTOR) seems to be significantly involved in the pathogenesis of the disease as well. mTOR, as a serine-threonine protein kinase, was previously known for controlling many cellular functions such as cell size, autophagy, and metabolism. In this regard, mammalian target of rapamycin complex 1 (mTORC1) may leave anti-aging impacts by robustly inhibiting autophagy, a mechanism that inhibits the accumulation of damaged protein aggregate and dysfunctional organelles. Formation and aggregation of neurofibrillary tangles and amyloid-beta plaques seem to be significantly regulated by mTOR signaling. Understanding the underlying mechanisms and connection between mTOR signaling and AD may suggest conducting clinical trials assessing the efficacy of rapamycin, as an mTOR inhibitor drug, in managing AD or may help develop other medications. In this literature review, we aim to elaborate mTOR signaling network mainly in the brain, point to gaps of knowledge, and define how and in which ways mTOR signaling can be connected with AD pathogenesis and symptoms.
Insights
Dysregulation of the mammalian target of rapamycin (mTOR) pathway is implicated in Alzheimer's disease (AD) pathogenesis. Investigating mTOR signaling in the brain may reveal new therapeutic targets for AD.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Alzheimer's disease (AD) is characterized by amyloid-beta plaques and tau tangles.
- The mammalian target of rapamycin (mTOR) pathway, a key regulator of cellular functions, is increasingly recognized for its role in AD pathogenesis.
Purpose of the Study:
- To elaborate on the mTOR signaling network within the brain.
- To identify knowledge gaps concerning mTOR signaling in AD.
- To define the connection between mTOR signaling and AD pathogenesis and symptoms.
Main Methods:
- Literature review focusing on mTOR signaling in the brain.
- Analysis of existing research on mTOR's role in cellular functions relevant to neurodegeneration.
- Exploration of the link between mTOR dysregulation and AD hallmarks.
Main Results:
- mTOR signaling significantly influences autophagy, a process critical for clearing protein aggregates.
- mTOR pathway dysregulation is linked to the formation and aggregation of amyloid-beta plaques and neurofibrillary tangles.
- mTORC1's inhibition of autophagy may have implications for cellular aging and protein aggregate accumulation.
Conclusions:
- Understanding the mTOR signaling network in the brain is crucial for elucidating AD mechanisms.
- Targeting mTOR signaling, potentially with rapamycin, could offer a novel therapeutic strategy for AD.
- Further research is needed to fully elucidate the complex interplay between mTOR and AD.
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